Top

Published in:

01-05-2021 | Original Research

Mechanism of Cyclic Tensile Stress in Osteogenic Differentiation of Human Periodontal Ligament Stem Cells

Authors: Xiayi Wu, Yi Li, Zeyuan Cao, Yunyi Xie, Chuanqiang Fu, Huan Chen

Published in: Calcified Tissue International | Issue 5/2021

Abstract

Human periodontal ligament stem cells (hPDLSCs) can undergo osteogenic differentiation under induction conditions. Cyclic tensile stress (CTS) can stimulate stem cell osteogenic differentiation. The present study explored the mechanism of CTS in hPDLSC osteogenic differentiation. The hPDLSCs of the 4th passage were selected. hPDLSCs were subjected to CTS with deformation of 10% elongation at 0.5 Hz for 1, 4, 8, 12 and 24 h. ALP activity and staining, ARS staining and detection of expressions of osteogenesis-related genes (RUNX2, OPN, Sp7 and OCN) were used to assess hPDLSC osteogenic differentiation ability. microRNA (miR)-129-5p and BMP2 expression and p-Smad1/5 level were detected under CTS stimulation. The binding relationship between miR-129-5p and BMP2 was predicted and verified. The osteogenic differentiation ability of CTS-treated hPDLSCs was evaluated after intervention of miR-129-5p and BMP2. CTS induced hPDLSC osteogenic differentiation, as manifested by increased ALP activities, osteogenesis-related gene expressions and mineralized nodules, together with positive ALP staining. CTS inhibited miR-129-5p expression, and promoted BMP2 expression and p-Smad1/5 level in hPDLSCs. miR-129-5p targeted BMP2. Overexpressed miR-129-5p or silenced BMP2 prevented hPDLSC osteogenic differentiation ability. We demonstrated that CTS inhibited miR-129-5p expression, and then activated the BMP2/Smad pathway, thereby showing stimulative effects on hPDLSC osteogenic differentiation.

Hyun SY, Lee JH, Kang KJ, Jang YJ (2017) Effect of FGF-2, TGF-beta-1, and BMPs on teno/ligamentogenesis and osteo/cementogenesis of human periodontal ligament stem cells. Mol Cells 40:550–557. https://doi.org/10.14348/molcells.2017.0019CrossRefPubMedPubMedCentral

Wei F, Yang S, Guo Q, Zhang X, Ren D, Lv T, Xu X (2017) MicroRNA-21 regulates osteogenic differentiation of periodontal ligament stem cells by targeting Smad5. Sci Rep 7:16608. https://doi.org/10.1038/s41598-017-16720-8CrossRefPubMedPubMedCentral

Xu Y, Qin W, Guo D, Liu J, Zhang M, Jin Z (2019) LncRNA-TWIST1 promoted osteogenic differentiation Bboth in PPDLSCs and in HPDLSCs by inhibiting TWIST1 expression. Biomed Res Int 2019:8735952. https://doi.org/10.1155/2019/8735952CrossRefPubMedPubMedCentral

Kim HY, Park SY, Choung SY (2018) Enhancing effects of myricetin on the osteogenic differentiation of human periodontal ligament stem cells via BMP-2/Smad and ERK/JNK/p38 mitogen-activated protein kinase signaling pathway. Eur J Pharmacol 834:84–91. https://doi.org/10.1016/j.ejphar.2018.07.012CrossRefPubMed

Zhang LN, Wang XX, Wang Z, Li KY, Xu BH, Zhang J (2019) Berberine improves advanced glycation end productsinduced osteogenic differentiation responses in human periodontal ligament stem cells through the canonical Wnt/betacatenin pathway. Mol Med Rep 19:5440–5452. https://doi.org/10.3892/mmr.2019.10193CrossRefPubMedPubMedCentral

McClarren B, Olabisi R (2018) Strain and vibration in mesenchymal stem cells. Int J Biomater 2018:8686794. https://doi.org/10.1155/2018/8686794CrossRefPubMedPubMedCentral

Charoenpanich A, Wall ME, Tucker CJ, Andrews DM, Lalush DS, Dirschl DR, Loboa EG (2014) Cyclic tensile strain enhances osteogenesis and angiogenesis in mesenchymal stem cells from osteoporotic donors. Tissue Eng Part A 20:67–78. https://doi.org/10.1089/ten.TEA.2013.0006CrossRefPubMed

Carroll SF, Buckley CT, Kelly DJ (2017) Cyclic tensile strain can play a role in directing both intramembranous and endochondral ossification of mesenchymal Sstem cells. Front Bioeng Biotechnol 5:73. https://doi.org/10.3389/fbioe.2017.00073CrossRefPubMedPubMedCentral

Bodle J, Hamouda MS, Cai S, Williams RB, Bernacki SH, Loboa EG (2019) Primary cilia exhibit mechanosensitivity to cyclic tensile strain and lineage-dependent expression in adipose-derived stem cells. Sci Rep 9:8009. https://doi.org/10.1038/s41598-019-43351-yCrossRefPubMedPubMedCentral

10.

Jiang Y, Wang Y, Tang G (2016) Cyclic tensile strain promotes the osteogenic differentiation of a bone marrow stromal cell and vascular endothelial cell co-culture system. Arch Biochem Biophys 607:37–43. https://doi.org/10.1016/j.abb.2016.08.015CrossRefPubMed

11.

Sun CX, Zhang LK, Feng XX, Zhao ZH (2011) Changes in the expression of Dlx5, Msx2, and Dlx5/Msx2 in hPDLSCs loaded with cyclic tensile stress. Sichuan Da Xue Xue Bao Yi Xue Ban 42:823–826PubMed

12.

Liu M, Sun F, Feng Y, Sun X, Li J, Fan Q, Liu M (2019) MicroRNA-132-3p represses Smad5 in MC3T3-E1 osteoblastic cells under cyclic tensile stress. Mol Cell Biochem 458:143–157. https://doi.org/10.1007/s11010-019-03538-3CrossRefPubMed

13.

Li X, Peng B, Zhu X, Wang P, Sun K, Lei X, He H, Tian Y, Mo S, Zhang R, Yang L (2019) MiR-210-3p inhibits osteogenic differentiation and promotes adipogenic differentiation correlated with Wnt signaling in ERalpha-deficient rBMSCs. J Cell Physiol 234:23475–23484. https://doi.org/10.1002/jcp.28916CrossRefPubMed

14.

Valenti MT, Dalle Carbonare L, Mottes M (2018) Role of microRNAs in progenitor cell commitment and osteogenic differentiation in health and disease (review). Int J Mol Med 41:2441–2449. https://doi.org/10.3892/ijmm.2018.3452CrossRefPubMed

15.

Shen H, Lu C, Shi J, Li H, Si J, Shen G (2019) Satb2 expression in Foxc1-promoted osteogenic differentiation of MC3T3-E1 cells is negatively regulated by microRNA-103-3p. Acta Biochim Biophys Sin (Shanghai) 51:588–597. https://doi.org/10.1093/abbs/gmz037CrossRef

16.

Gu X, Li M, Jin Y, Liu D, Wei F (2017) Identification and integrated analysis of differentially expressed lncRNAs and circRNAs reveal the potential ceRNA networks during PDLSC osteogenic differentiation. BMC Genet 18:100. https://doi.org/10.1186/s12863-017-0569-4CrossRefPubMedPubMedCentral

17.

Raimondo S, Urzi O, Conigliaro A, Bosco GL, Parisi S, Carlisi M, Siragusa S, Raimondi L, Luca A, Giavaresi G, Alessandro R (2020) Extracellular vesicle microRNAs contribute to the osteogenic inhibition of mesenchymal stem cells in multiple Mmyeloma. Cancers (Basel). https://doi.org/10.3390/cancers12020449CrossRef

18.

Liu K, Huang J, Ni J, Song D, Ding M, Wang J, Huang X, Li W (2017) MALAT1 promotes osteosarcoma development by regulation of HMGB1 via miR-142-3p and miR-129-5p. Cell Cycle 16:578–587. https://doi.org/10.1080/15384101.2017.1288324CrossRefPubMedPubMedCentral

19.

Suzuki R, Nemoto E, Shimauchi H (2014) Cyclic tensile force up-regulates BMP-2 expression through MAP kinase and COX-2/PGE2 signaling pathways in human periodontal ligament cells. Exp Cell Res 323:232–241. https://doi.org/10.1016/j.yexcr.2014.02.013CrossRefPubMed

20.

Xu Y, Ren C, Zhao X, Wang W, Zhang N (2019) microRNA-132 inhibits osteogenic differentiation of periodontal ligament stem cells via GDF5 and the NF-kappaB signaling pathway. Pathol Res Pract 215:152722. https://doi.org/10.1016/j.prp.2019.152722CrossRefPubMed

21.

Zhou N, Li Q, Lin X, Hu N, Liao JY, Lin LB, Zhao C, Hu ZM, Liang X, Xu W, Chen H, Huang W (2016) BMP2 induces chondrogenic differentiation, osteogenic differentiation and endochondral ossification in stem cells. Cell Tissue Res 366:101–111. https://doi.org/10.1007/s00441-016-2403-0CrossRefPubMed

22.

Li H, Nie B, Du Z, Zhang S, Long T, Yue B (2018) Bacitracin promotes osteogenic differentiation of human bone marrow mesenchymal stem cells by stimulating the bone morphogenetic protein-2/Smad axis. Biomed Pharmacother 103:588–597. https://doi.org/10.1016/j.biopha.2018.04.084CrossRefPubMed

23.

Kato RB, Roy B, De Oliveira FS, Ferraz EP, De Oliveira PT, Kemper AG, Hassan MQ, Rosa AL, Beloti MM (2016) Erratum: Nanotopography Directs Mesenchymal stem cells to osteoblast lineage through regulation of microRNA-SMAD-BMP-2 circuit. J Cell Physiol 231:2548. https://doi.org/10.1002/jcp.25474CrossRef

24.

Li L, Han MX, Li S, Xu Y, Wang L (2014) Hypoxia regulates the proliferation and osteogenic differentiation of human periodontal ligament cells under cyclic tensile stress via mitogen-activated protein kinase pathways. J Periodontol 85:498–508. https://doi.org/10.1902/jop.2013.130048CrossRefPubMed

25.

Wang P, Wang Y, Tang W, Wang X, Pang Y, Yang S, Wei Y, Gao H, Wang D, Cao Z (2017) Bone morphogenetic protein-9 enhances osteogenic differentiation of human periodontal ligament stem cells via the JNK pathway. PLoS ONE 12:e0169123. https://doi.org/10.1371/journal.pone.0169123CrossRefPubMedPubMedCentral

26.

Yu N, Prodanov L, te Riet J, Yang F, Walboomers XF, Jansen JA (2013) Regulation of periodontal ligament cell behavior by cyclic mechanical loading and substrate nanotexture. J Periodontol 84:1504–1513. https://doi.org/10.1902/jop.2012.120513CrossRefPubMed

27.

Zhang M, Bian YQ, Tao HM, Yang XF, Mu WD (2018) Simvastatin induces osteogenic differentiation of MSCs via Wnt/beta-catenin pathway to promote fracture healing. Eur Rev Med Pharmacol Sci 22:2896–2905. https://doi.org/10.26355/eurrev_201805_14992CrossRefPubMed

28.

Zhu XX, Yan YW, Chen D, Ai CZ, Lu X, Xu SS, Jiang S, Zhong GS, Chen DB, Jiang YZ (2016) Long non-coding RNA HoxA-AS3 interacts with EZH2 to regulate lineage commitment of mesenchymal stem cells. Oncotarget 7:63561–63570. https://doi.org/10.18632/oncotarget.11538CrossRefPubMedPubMedCentral

29.

Ye Y, Du Y, Guo F, Gong C, Yang K, Qin L (2012) Comparative study of the osteogenic differentiation capacity of human bone marrow- and human adipose-derived stem cells under cyclic tensile stretch using quantitative analysis. Int J Mol Med 30:1327–1334. https://doi.org/10.3892/ijmm.2012.1123CrossRefPubMed

30.

Valenti MT, Deiana M, Cheri S, Dotta M, Zamboni F, Gabbiani D, Schena F, Dalle Carbonare L, Mottes M (2019) Physical exercise modulates miR-21-5p, miR-129-5p, miR-378-5p, and miR-188-5p expression in progenitor cells promoting osteogenesis. Cells. https://doi.org/10.3390/cells8070742CrossRefPubMedPubMedCentral

31.

Chen Y, Huang W, Sun W, Zheng B, Wang C, Luo Z, Wang J, Yan W (2018) LncRNA MALAT1 promotes cancer metastasis in osteosarcoma via activation of the PI3K-Akt signaling pathway. Cell Physiol Biochem 51:1313–1326. https://doi.org/10.1159/000495550CrossRefPubMed

32.

Zhang P, Li J, Song Y, Wang X (2017) MiR-129-5p inhibits proliferation and invasion of chondrosarcoma cells by regulating SOX4/Wnt/beta-catenin signaling pathway. Cell Physiol Biochem 42:242–253. https://doi.org/10.1159/000477323CrossRefPubMed

33.

Shi ZL, Zhang H, Fan ZY, Ma W, Song YZ, Li M, Li TQ, Cao SX, Feng GJ (2020) Long noncoding RNA LINC00314 facilitates osteogenic differentiation of adipose-derived stem cells through the hsa-miR-129-5p/GRM5 axis via the Wnt signaling pathway. Stem Cell Res Ther 11:240. https://doi.org/10.1186/s13287-020-01754-zCrossRefPubMedPubMedCentral

34.

Liou SF, Hsu JH, Chu HC, Lin HH, Chen IJ, Yeh JL (2015) KMUP-1 Promotes osteoblast differentiation through cAMP and cGMP pathways and signaling of BMP-2/Smad1/5/8 and Wnt/beta-catenin. J Cell Physiol 230:2038–2048. https://doi.org/10.1002/jcp.24904CrossRefPubMed

35.

Li Z, Wang W, Xu H, Ning Y, Fang W, Liao W, Zou J, Yang Y, Shao N (2017) Effects of altered CXCL12/CXCR4 axis on BMP2/Smad/Runx2/Osterix axis and osteogenic gene expressions during osteogenic differentiation of MSCs. Am J Transl Res 9:1680–1693PubMedPubMedCentral

36.

Wang M, Li J, Ye Y, He S, Song J (2020) SHED-derived conditioned exosomes enhance the osteogenic differentiation of PDLSCs via Wnt and BMP signaling in vitro. Differentiation 111:1–11. https://doi.org/10.1016/j.diff.2019.10.003CrossRefPubMed

37.

Yang W, Sun P (2019) Downregulation of microRNA-129-5p increases the risk of intervertebral disc degeneration by promoting the apoptosis of nucleus pulposus cells via targeting BMP2. J Cell Biochem 120:19684–19690. https://doi.org/10.1002/jcb.29274CrossRefPubMed

38.

Liu X, Deng X, Ding R, Cheng X, Jia J (2020) Chondrocyte suppression is mediated by miR-129-5p via GDF11/SMAD3 signaling in developmental dysplasia of the hip. J Orthop Resdoi. https://doi.org/10.1002/jor.24713CrossRef

39.

Kim KM, Kim DY, Lee DS, Kim JW, Koh JT, Kim EJ, Jang WG (2019) Peroxiredoxin II negatively regulates BMP2-induced osteoblast differentiation and bone formation via PP2A Calpha-mediated Smad1/5/9 dephosphorylation. Exp Mol Med 51:1–11. https://doi.org/10.1038/s12276-019-0263-xCrossRefPubMedPubMedCentral

Title: Mechanism of Cyclic Tensile Stress in Osteogenic Differentiation of Human Periodontal Ligament Stem Cells
Authors: Xiayi Wu
Yi Li
Zeyuan Cao
Yunyi Xie
Chuanqiang Fu
Huan Chen
Publication date: 01-05-2021
Publisher: Springer US
Published in: Calcified Tissue International / Issue 5/2021
Print ISSN: 0171-967X
Electronic ISSN: 1432-0827
DOI: https://doi.org/10.1007/s00223-020-00789-x

Live Webinar | 27-06-2024 | 18:00 (CEST)

Keynote webinar | Spotlight on medication adherence

Reserve your place

Live: Thursday 27th June 2024, 18:00-19:30 (CEST)

WHO estimates that half of all patients worldwide are non-adherent to their prescribed medication. The consequences of poor adherence can be catastrophic, on both the individual and population level.

Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.

Prof. Kevin Dolgin

Prof. Florian Limbourg

Prof. Anoop Chauhan

Developed by: Springer Medicine

Obesity Clinical Trial Summary

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.

Developed by: Springer Medicine

Highlights from the ACC 2024 Congress

Year in Review: Pediatric cardiology

Pediatric Cardiology Video

Watch Dr. Anne Marie Valente present the last year's highlights in pediatric and congenital heart disease in the official ACC.24 Year in Review session.

Year in Review: Pulmonary vascular disease

Cardiopulmonary Comorbidity Video

The last year's highlights in pulmonary vascular disease are presented by Dr. Jane Leopold in this official video from ACC.24.

Year in Review: Valvular heart disease

Valvular Heart Disease Video

Watch Prof. William Zoghbi present the last year's highlights in valvular heart disease from the official ACC.24 Year in Review session.

Year in Review: Heart failure and cardiomyopathies

Heart Failure Video

Watch this official video from ACC.24. Dr. Biykem Bozkurt discusses last year's major advances in heart failure and cardiomyopathies.

ACC 2024 Congress Coverage

Year in Review: Heart failure and cardiomyopathies

Heart Failure Video

Watch this official video from ACC.24. Dr. Biykem Bozkurt discusses last year's major advances in heart failure and cardiomyopathies.

Watch now

Semaglutide benefits people with type 2 diabetes and obesity-related heart failure

16-04-2024 Type 2 Diabetes News

Incentivised to exercise

11-04-2024 Lifestyle Modifications News

New intervention for STEMI-related cardiogenic shock

10-04-2024 Myocardial Infarction News

» View more highlights on the ACC 2024 congress hub page

Image Credits

Illustration of figure on mountain summit/© Orapun / Stock.adobe.com, STEP AAG HeroTeaserCollection image/© Tarek / Generated with AI / Stock.adobe.com, ACC 2024 Pediatric and Congenital Heart Disease: Year in Review/© 2024 American College of Cardiology, ACC 2024 Pulmonary Vascular Disease: Year in Review/© 2024 American College of Cardiology, ACC 2024 Valvular Heart Disease: Year in Review/© 2024 American College of Cardiology, ACC 2024 HF and Cardiomyopathies: Year in Review/© 2024 American College of Cardiology, Woman out walking/© Seventyfour / stock.adobe.com (symbolic image with model), Woman checking smartwatch /© saltdium / stock.adobe.com (symbolic image with model), Cardiac catheterization/© Damian / stock.adobe.com

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Please log in to get access to this content

Other articles of this Issue 5/2021

An Exopolysaccharide Produced by Bifidobacterium longum 35624® Inhibits Osteoclast Formation via a TLR2-Dependent Mechanism

Positive Effect of Teriparatide on Areal Bone Mineral Density in Young Women with Anorexia Nervosa: A Pilot Study

Paget’s Disease of the Bone: Patterns of Referral to Secondary Care Following Diagnosis on X-rays

Does Genotype–Phenotype Correlation Exist in Vitamin D-Dependent Rickets Type IA: Report of 13 New Cases and Review of the Literature

Combined Biomaterials: Amniotic Membrane and Adipose Tissue to Restore Injured Bone as Promoter of Calcification in Bone Regeneration: Preclinical Model

Comparative Effect of Zoledronate at 6 Versus 18 Months Following Denosumab Discontinuation

Live: Thursday 27th June 2024, 18:00-19:30 (CEST)

Highlights from the ACC 2024 Congress

ACC 2024 Congress Coverage